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Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma
Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. F...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156787/ https://www.ncbi.nlm.nih.gov/pubmed/32061138 http://dx.doi.org/10.1111/cas.14352 |
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author | Tachita, Takuto Kinoshita, Shiori Ri, Masaki Aoki, Sho Asano, Arisa Kanamori, Takashi Yoshida, Takashi Totani, Haruhito Ito, Asahi Kusumoto, Shigeru Komatsu, Hirokazu Yamagata, Kazufumi Kubo, Kohmei Tohkin, Masahiro Fukuda, Shinsaku Iida, Shinsuke |
author_facet | Tachita, Takuto Kinoshita, Shiori Ri, Masaki Aoki, Sho Asano, Arisa Kanamori, Takashi Yoshida, Takashi Totani, Haruhito Ito, Asahi Kusumoto, Shigeru Komatsu, Hirokazu Yamagata, Kazufumi Kubo, Kohmei Tohkin, Masahiro Fukuda, Shinsaku Iida, Shinsuke |
author_sort | Tachita, Takuto |
collection | PubMed |
description | Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. Forty‐eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post‐Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN‐pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post‐Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy. |
format | Online Article Text |
id | pubmed-7156787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71567872020-04-20 Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma Tachita, Takuto Kinoshita, Shiori Ri, Masaki Aoki, Sho Asano, Arisa Kanamori, Takashi Yoshida, Takashi Totani, Haruhito Ito, Asahi Kusumoto, Shigeru Komatsu, Hirokazu Yamagata, Kazufumi Kubo, Kohmei Tohkin, Masahiro Fukuda, Shinsaku Iida, Shinsuke Cancer Sci Original Articles Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. Forty‐eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post‐Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN‐pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post‐Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy. John Wiley and Sons Inc. 2020-03-12 2020-04 /pmc/articles/PMC7156787/ /pubmed/32061138 http://dx.doi.org/10.1111/cas.14352 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Tachita, Takuto Kinoshita, Shiori Ri, Masaki Aoki, Sho Asano, Arisa Kanamori, Takashi Yoshida, Takashi Totani, Haruhito Ito, Asahi Kusumoto, Shigeru Komatsu, Hirokazu Yamagata, Kazufumi Kubo, Kohmei Tohkin, Masahiro Fukuda, Shinsaku Iida, Shinsuke Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
title | Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
title_full | Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
title_fullStr | Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
title_full_unstemmed | Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
title_short | Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
title_sort | expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156787/ https://www.ncbi.nlm.nih.gov/pubmed/32061138 http://dx.doi.org/10.1111/cas.14352 |
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